| abstract |
The present invention relates to new methods of synthesis, which allow to obtain previously unavailable substituted tetracycline analogs, which have high antibacterial activity. The methods described in the present invention utilize reactive precursors of tetracycline, reactive precursors of an organic substituent, and transition metal catalysts under conditions that form a substituted tetracycline derivative containing the desired organic substituent. In one embodiment of the invention, the substituted tetracycline analog can be obtained by mixing a reactive precursor of tetracycline, such as the isoniazionium salt of tetracycline, and a reactive precursor of an organic substituent, for example, alkenes, substituted alkenes, vinyl monomers, aromatic and heteroaromatic compounds, in the presence of a catalyst based on a transitional a metal such as palladium chloride under the conditions under which the tetracycline analog is formed, substituted organic substituent. Such substituted analogs may optionally be used as intermediates for the preparation of other compounds, for example, in the hydrogenation of unsaturated substituent groups. |